B-cell Superantigens in Health & Disease | NYU Langone Health

Skip to Main Content
B-cell Immunobiology Lab Research B-cell Superantigens in Health & Disease

B-cell Superantigens in Health & Disease

For many years the B-cell Immunobiology Lab has pioneered investigations of the molecular pathways responsible for the in vivo effects of exposure to a B-cell superantigen. Using the prototypic superantigen, Staphylococcal protein A (SpA), as a model system to understand how different B-cell antigen receptor encounters lead to lymphocyte activation, proliferation, or apoptotic deletion, we have studied a class of natural microbial toxins that we have demonstrated can act as superantigens affecting large sets of B-cells, defined by their antibody variable region gene usage.

We have shown how in vivo encounters with SpA (see Figure 1), can result in targeted activation-induced cell death. We also identified the exact intrinsic pathway of apoptosis and demonstrated the requirement for a single pro-death Bcl-2 family member, Bim. Parallel studies are in progress to assess similarities and differences for CD20 mediated B-cell deletion occurring after therapeutic treatments with rituxan. These studies are relevant to understanding and developing better therapeutic agents for the selective targeting and deletion of malignant B-cell populations in models of lymphoma and leukemia.

Deconvolved Digital Images of T15i Splenic B cells 8 h After Control or SpA Treatment
Figure 1: SpA induces Bim expression in the cytoplasm of a VH3 BCR expressing B-cell. Deconvolved digital images of T15i splenic B cells 8 h after control (A–C) or SpA treatment (D–F). Cells were 4′-diamidino-2-phenylindole stained for nuclei (blue), anti-IgM (red), and anti-Bim (green). A and D, Nuclear staining and surface anti-IgM are shown, while in B and E nuclear staining and anti-Bim are shown. C and F, A merge of all colors. G, At 8 h after SpA treatment, cells were stained for the nuclear envelope anti-lamina A/C (blue) and Bim (green).

Unexpectedly, the bacterial commensal that identified as an overrepresented pathbiont, Ruminococcus (Blautia) gnavus, in Lupus nephritis (Azzouz et al., 2019, Ann Rheum Dis), was recently found to release a distinct B-cell superantigen into the gut of colonized humans. Sequence analysis indicates that the properties of this microbial factor, that are akin to those of SpA, arose by convergent evolution. We are currently investigating how this factor may contribute to the pathogenesis of clinical lupus nephritis.